Carbapenem-resistant Gram-negative Bacilli Research Articles

Bacteremic nosocomial pneumonia caused by Gram-negative bacilli: results from the nationwide ALARICO study in Italy.

To describe the clinical characteristics and outcomes of patients with nosocomial pneumonia (NP) causedby carbapenem-resistant Gram-negative bacilli (CR-GNB) and to compare them to patients with NP causedby carbapenem-susceptible (CS)-GNB. Prospective observational multicenter study including patients with bacteremic NP caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated. Overall, 167 patients with GNB NP were included: 101 with bacteremic NP causedby CR-GNB (n = 39 by KPC-producing Klebsiella pneumoniae, n = 29 by carbapenem-resistant Acinetobacter baumannii, n = 28 by carbapenem-resistant Pseudomonas aeruginosa, n = 5 by MBL-producing Klebsiella pneumoniae) and 66 cases of bacteremic CS-GNB NP. Thirty-day mortality rate was higher in patients with NP causedby CR-GNB compared to those with NPcausedby CS-GNB (46.5% vs 30.3%, p = 0.036). On multivariable analysis, age (HR 1.044, 95% CI 1.021-1.067, p < 0.001), hematological malignancy (HR 4.307, 95% CI 1.924-9.643, p < 0.001) and septic shock (HR 3.668, 95% CI 2.001-6.724, p < 0.001) were factors independently associated with 30-day mortality, while the receipt of adequate antibiotic therapy within 24h from infection onset (HR 0.495, 95% CI 0.252-0.969, p = 0.04) was a protective factor. Carbapenem resistance was not associated with increased risk of mortality (HR 1.075, 95% CI 0.539-2.142, p = 0.837). Patients with bacteremic NP causedby CR-GNB have high mortality rate. Strategies to reduce the time from infection to the administration of adequate antibiotic therapy should be implemented in patients with NP.

Detection of carbapenemases in Enterobacterales and other Gram-negative bacilli recovered from hospital and municipal wastewater in Mexico City

Wastewater serves as a reservoir for antimicrobial-resistant bacteria. This study revealed the presence of carbapenem-resistant and carbapenemase-producing Gram-negative bacilli (GNB), established clonal relationships among isolates in hospital and municipal wastewater, and identified a high-risk clone in municipal wastewater. A total of 63 isolates of GNB were obtained, with Enterobacterales being the most frequently isolated group (62%). Carbapenemase-producing Lelliottia amnigena, Kluyvera cryocrescens, and Shewanella putrefaciens isolates were documented for the first time in Mexico. The detectableted carbapenemase genes were blaKPC (55%), blaNDM (12%), blaVIM−2 (12%), blaOXA−48 (4%), blaGES (2%), blaNDM−1 (2%), and blaNDM−5 (2%). Clonal relationships were observed among Klebsiella pneumoniae and Enterobacter spp. isolates, and remarkably the high-risk clone Escherichia coli ST361, carrying blaNDM−5, was identified. This study demonstrates that wastewater harbours carbapenem-resistant and carbapenemase-producing bacteria, posing a public health threat that requires epidemiological surveillance.

Epidemiology of Bacteremia in Patients with Hematological Malignancies and Hematopoietic Stem Cell Transplantation and the Impact of Antibiotic Resistance on Mortality: Data from a Multicenter Study in Argentina.

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin-tazobactam: 31.05% vs. 45.2% (p < 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.

Tigecycline Resistant Pattern among Carbapenem Resistant Gram-negative Bacilli: Prospective Cross-sectional Study

Introduction: Tigecycline is a unique tetracycline class of semi-synthetic, last-line broad spectrum antibiotic against multi-drug-resistant bacteria. However, recently, resistance to this antibiotic is on the rise. Aims: This study was conducted to determine the prevalence of tigecycline resistance amongst carbapenem-resistant Gram-negative bacilli (GNB) isolated from clinical samples (pus and sputum) as well as to evaluate their antimicrobial susceptibility pattern. Study design: Prospective cross sectional Place and Duration of Study: Department of Microbiology at Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow, between January 2023 and December 2023. Methodology: Identification of GNB grown on culture was done by conventional biochemical tests and later validated by MALDI-TOF MS. The antimicrobial sensitivity testing of isolates was done using the E-test, and disk diffusion method. Minimum inhibitory concentration determination was done by Broth micro-dilution (BMD) method. Results: Amongst 8326 pus and respiratory samples, GNBs were recovered from 63.15% (5258/8326). Of 5258 GNB isolates, 50.74% (2668) were carbapenem-resistant, while 7.85% (413) demonstrated resistance to both tigecycline and carbapenem. Common isolates in this group were Klebsiella pneumoniae (37.04%), Acinetobacter spp. (25.18%), Enterobacter spp. (14.28%) and Escherichia coli (12.59%). BMD results demonstrated highest activity of tigecycline against carbapenem-resistant E. coli, followed by Citrobacter and Enterobacter. It works against resistant strains of Acinetobacter baumannii and K. pneumoniae as well, but in higher concentrations. Conclusion: High tigecycline resistance (one of the last-resort drugs) among carbapenem resistant GNB isolates is a matter of clinical concern, leaving physicians with limited options for treatment of such infections. Proper adherence to the policies of antimicrobial stewardship programs can reduce the emergence of resistance.

Multicenter evaluation of activity of aztreonam in combination with avibactam, relebactam, and vaborbactam against metallo-β-lactamase-producing carbapenem-resistant gram-negative bacilli.

Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-β-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and Stenotrophomonas maltophilia. However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the in vitro activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and S. maltophilia using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and S. maltophilia (ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and S. maltophilia (ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and S. maltophilia, ATM-IMI-REL might be a reasonable alternative.

Assessment of in vitro antimicrobial activity of ceftazidime-avibactam and phenotypic synergy testing with aztreonam against carbapenem resistant Gram-negative bacilli in a tertiary care hospital

Objectives: Ceftazidime avibactam (CZA) is a drug used against carbapenemase producing Gram-negative bacterial infections. Avibactam (AVI) is a non-beta-lactam-beta-lactamase inhibitor which has no action against metallo-β-lactamase (MBL) enzymes. This inadequacy is counteracted by combining CZA with aztreonam (ATM). The present study aims to denote the in vitro susceptibility pattern of the CZA and CZA-ATM combination in our area. Materials and Methods: In this study conducted prospectively from January to June 2023, the samples growing Enterobacterales and Pseudomonas aeruginosa were proceeded for carbapenemase detection by phenotypic testing for EDTA carbapenem inactivation method and modified carbapenem inactivation method. The minimum inhibitory concentration MIC of CZA was determined by E-strip and interpreted as per clinical and laboratory standard institute (CLSI) guidelines, while synergy testing of CZA and ATM was performed using ATM discs. Statistical Analysis: All data were entered in Microsoft Excel and analyzed for basic statistics. Results: The study included 150 carbapenem resistant organisms (131 Enterobactarales and 19 P. aeruginosa). Among these Enterobacterale strains, 72 (54.9%) were MBL producers. CZA resistance was detected in 69.3% of Klebsiella spp., 61.53% of Escherichia coli, and 50% of Serratia spp. Among Klebsiella spp. and E. coli, 88.9% and 65.2% of MBL isolates showed in vitro synergy to CZA-ATM. Conclusions: The study highlights a good in vitro sensitivity pattern of the CZA and ATM combination. However, we also highlight a growing percentage of non-synergistic interactions that need further genetic evaluation.

Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study.

Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

Molecular Detection of Carbapenemase Genes among Carbapenem Resistant Gram-Negative Bacilli in Tertiary Care Hospital, Bangladesh

Molecular Detection of Carbapenemase Genes among Carbapenem Resistant Gram-Negative Bacilli in Tertiary Care Hospital, Bangladesh

Detection of KPC directly from positive blood cultures by MALDI-TOF: From research to the clinical microbiology laboratory routine

Bloodstream infections (BSI) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) are a subject of major clinical concern, mainly those associated with carbapenemase-producing isolates. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed to detect specific β-lactamases, including KPC. We aimed to detect KPC enzyme directly from positive blood cultures using MALDI-TOF MS. Overall, 146 clinical Gram-negative bacilli (46 CR-GNB) recovered from consecutive blood cultures were evaluated. Proteins were extracted using formic acid, isopropyl alcohol, and water and spotted onto a steel target plate using the double-layer sinapinic acid method. The relative ions intensity ≥120 arbitrary units (a.u.) of a peak close to 28,700 m/z indicated the presence of KPC. The results were compared to HRM-qPCR methodology. This specific peak was observed in 11/14 blood bottles with blaKPC positive isolates (78.6% sensitivity), with 3 false-positive results (97.7% specificity). Analysis from colonies reached identical sensitivity (78.6%), but higher specificity (100%). The detection of KPC peaks directly from positive blood cultures using MALDI-TOF MS is feasible and rapid. It's excellent specificity indicates that positive results are consistently associated with the presence of a KPC producer in positive blood culture.

Molecular epidemiology of carbapenem-resistant gram-negative bacilli in Ecuador

IntroductionCarbapenem-resistant gram-negative bacilli are a worldwide concern because of high morbidity and mortality rates. Additionally, the increasing prevalence of these bacteria is dangerous. To investigate the extent of antimicrobial resistance and prioritize the utility of novel drugs, we evaluated the molecular characteristics and antimicrobial susceptibility profiles of carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii in Ecuador in 2022.MethodsNinety-five clinical isolates of carbapenem non-susceptible gram-negative bacilli were collected from six hospitals in Ecuador. Carbapenem resistance was confirmed with meropenem disk diffusion assays following Clinical Laboratory Standard Institute guidelines. Carbapenemase production was tested using a modified carbapenemase inactivation method. Antimicrobial susceptibility was tested with a disk diffusion assay, the Vitek 2 System, and gradient diffusion strips. Broth microdilution assays were used to assess colistin susceptibility. All the isolates were screened for the blaKPC,blaNDM,blaOXA-48,blaVIM and blaIMP genes. In addition, A. baumannii isolates were screened for the blaOXA-23, blaOXA-58 and blaOXA-24/40 genes.ResultsCarbapenemase production was observed in 96.84% of the isolates. The blaKPC, blaNDM and blaOXA-48 genes were detected in Enterobacterales, with blaKPC being predominant. The blaVIM gene was detected in P. aeruginosa, and blaOXA-24/40 predominated in A. baumannii. Most of the isolates showed co-resistance to aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. Both ceftazidime/avibactam and meropenem/vaborbactam were active against carbapenem-resistant gram-negative bacilli that produce serin-carbapenemases.ConclusionThe epidemiology of carbapenem resistance in Ecuador is dominated by carbapenemase-producing K. pneumoniae harbouring blaKPC. Extensively drug resistant (XDR) P. aeruginosa and A. baumannii were identified, and their identification revealed the urgent need to implement strategies to reduce the dissemination of these strains.

Traitement des infections dues à des bacilles à Gram négatif en pédiatrie

Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly β-lactams, is now considered as major public health problem. The main resistance mechanisms to β-lactams in Enterobacterales are the production of extended spectrum β-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all β-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new β-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited.

International guidelines for the treatment of carbapenem-resistant Gram-negative Bacilli infections: A comparison and evaluation

ObjectivesThis study aimed to appraise clinical practice guidelines (CPGs) for the treatment of carbapenem-resistant Gram-negative Bacilli (CRGNB) infections and to summarise the recommendations. MethodsA systematic search of the literature published from January 2012 to March 2023 was undertaken to identify CPGs related to CRGNB infections treatment. The methodological and reporting quality of eligible CPGs were assessed using six domains of the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and seven domains of the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist. Basic information and recommendations of included CPGs were extracted and compared. ResultsA total of 21 CPGs from 7953 relevant articles were included. The mean overall AGREE II score was 62.7%, and was highest for “clarity of presentation” (90.2%) and lowest for “stakeholder involvement” (44.8%). The overall reporting quality of all of the CPGs was suboptimal, with the proportion of eligible items ranging from 45.7 to 85.7%. The treatment of CRGNB infections is related to the type of pathogen, the sensitivity of antimicrobial agents, and the site of infection. In general, the recommended options mainly included novel β-lactam/ β-lactamase inhibitors, cefiderocol, ampicillin-sulbactam (mainly for carbapenem-resistant Acinetobacter baumannii [CRAB]), and combination therapy, involving polymyxin B/colistin, tigecycline (except for carbapenem-resistant Pseudomonas aeruginosa), aminoglycosides, carbapenems, fosfomycin, and sulbactam (mainly for CRAB). ConclusionsThe methodological and reporting quality of CPGs for the treatment of CRGNB infections are generally suboptimal and need further improvement. Both monotherapy with novel drugs and combination therapy play important roles in the treatment.

Frequency of Multidrug-Resistant Microorganisms Associated with Bacterial Coinfections in Hospitalized Patient with Covid-19: A Literature Review

Patients with a doença do coronavírus 2019 (COVID-19) may be at risk of associated bacterial co-infections, and the involvement of multidrug-resistant (MDR) microorganisms in these cases can lead to an increase in morbidity and mortality rates. The objective of this study was to describe the frequency of the main MDR microorganisms associated with bacterial co-infections in patients hospitalized with COVID-19. To this end, we carried out a search in the PubMed and Regional Portal of the Virtual Health Library (VHL) databases, from December 2019 to September 2023, with the keywords COVID-19, co-infection and multidrug-resistant microorganism. Of the 535 articles initially found, only 14 were selected for analysis. Gram-negative bacteria were most frequently involved in bacterial co-infections in patients with COVID-19 (70%). Among these, Klebsiella pneumoniae and Acinetobacter baumannii predominated, with 85.71% and 78.57%, respectively. Among gram-positive bacteria, Staphylococcus aureus (71.42%) was the most common. Among MDR microorganisms, the prevalent species were carbapenem-resistant gram-negative bacilli (32%) and methicillin-resistant S. aureus (85.7%). Furthermore, a higher frequency of MDR microorganisms was observed in patients with COVID-19 in intensive care units (ICU). Thus, the findings of the present study indicate the need for attention to infections caused by multidrug-resistant microorganisms in critically ill patients with COVID-19.

Epidemiology and clinical characteristics of patients with healthcare-acquired multidrug-resistant Gram-negative bacilli: a retrospective study from a tertiary care hospital

The numbers of infections caused by Gram-negative bacteria (GNB) that produce extended-spectrum beta-lactamases (ESBLs) and those that are carbapenem resistant, especially Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are increasing, and these infections are becoming a global public health problem. The aim of this study was to assess the prevalence of infections caused by ESBL-producing and carbapenem-resistant Gram-negative bacilli in patients hospitalized at An-Najah National University Hospital in Nablus, Palestine, and to provide healthcare workers with valuable information on the treatment of these infections. A retrospective cross-sectional investigation was conducted at a large tertiary care teaching hospital. The study included patients admitted to the hospital between January and December 2021, from whom ESBL-producing and carbapenem-resistant Gram-negative bacilli were isolated. The patients' clinical and demographic information was obtained from the hospital information system. In addition, information regarding the bacterial isolates and antibiotic resistance was obtained from the hospital's microbiology laboratory. This study included a total of 188 patients—91 males (48.4%) and 97 females (51.6%). The general surgical ward accounted for the highest proportion of infections (30.9%), followed by the surgical ICU (12.2%). The most common infections were caused by ESBL-producing E. coli, which accounted for 62.8% of the cases. Among them, urinary tract infections caused by this microorganism were the most prevalent (44.7% of patients). Over 50% of the patients (54.2%) had a history of antibiotic use, and 77.8% had been hospitalized within the past three months. ESBL-producing E. coli was significantly isolated from blood cultures (p-value = 0.000), and CR-K. pneumoniae was significantly isolated from endotracheal isolates (p-value = 0.001). This study emphasizes the concerning frequency of healthcare-acquired infections caused by ESBL-producing and carbapenem-resistant GNB in a tertiary care hospital. The substantial prevalence of antibiotic resistance presents considerable obstacles to the successful administration of routinely employed antibiotics. The results highlight the immediate need for improved antimicrobial stewardship and the implementation of infection control strategies to reduce the effects of multidrug-resistant GNB on patient well-being and public health.

Comparative study of colistin methanesulfonate and colistin sulfate/polymyxin B in the treatment of ceftazidime-avibactam resistant Gram-negative bacilli infections

ObjectiveTo evaluate the clinical efficacy of different species of polymyxin drugs in the treatment of Carbapenem-Resistant Gram-negative bacilli (CR-GNB) resistant to ceftazidime-avibactam (CZA). MethodsPatients infected by CR-GNB strains and treated with polymyxin drugs were selected and divided into colistin methanesulfonate (CMS) group and colistin sulfate/polymyxin B (CSPB) group to observe clinical efficacy and safety. Results65 patients were eventually included (CMS group, n ​= ​29; CSPB group, n ​= ​36). The clinical efficacy, microbiological eradication rate and 28-day mortality between the two groups were similar, with no statistical significance (51.72% vs. 50.00%, p ​= ​0.890; 55.17% vs. 52.78%, p ​= ​0.847; 17.24% vs. 25.00%, p ​= ​0.449). With regard to renal safety, the incidence of acute kidney injury (AKI) in the CMS group was significantly higher than that in the CSPB group (34.48% vs. 5.56%, p ​= ​0.003). Among them, the incidence of AKI grade 3 in the CMS group tended to be higher than that in the CSPB group (24.14% vs. 5.56%, p ​= ​0.066). ConclusionThe results based on small sample size from a single center showed that clinical response to the treatment of ceftazidime-avibactam resistant Gram-negative bacillus infections is similar for CMS and Colistin Sulfate/Polymyxin B, but the nephrotoxicity of CMS is greater than that of polymyxin sulfates.

Ceftazidime-avibactam/aztreonam combination synergy against carbapenem-resistant Gram-negative isolates: In vitro study

ABSTRACT Background: The ceftazidime-avibactam combination is able to inhibit ESBLs, AmpCs and Class A carbapenemases and has been recommended for the treatment of complicated UTIs and ventilator-associated bacterial pneumonia. Aims: The present study was undertaken to evaluate the in vitro activity of ceftazidime-avibactam and to determine the synergistic activity of aztreonam/ceftazidime-avibactam combination against carbapenem-resistant Gram-negative bacilli. Materials and Methods: Gram-negative isolates that exhibited resistance to at least one of the carbapenems (imipenem or meropenem) by the Kirby–Bauer disc diffusion method were subjected to phenotypic characterisation by the Vitek-2 automated method. Phenotypically confirmed isolates were subjected to ceftazidime/avibactam-aztreonam synergy testing by disc diffusion method. Results: Twenty-two carbapenem-resistant isolates showed a minimum inhibitory concentration of 4–64 μg/mL for imipenem and 8–64 μg/mL for meropenem. Out of 22 carbapenem-resistant isolates, 18 (81.82%) isolates showed resistance to ceftazidime-avibactam and aztreonam, and 2 (9.09%) isolates showed intermediate resistance to aztreonam. Nine (40.91%) isolates showed synergy to ceftazidime-avibactam/aztreonam combination by disc diffusion method. An increase in zone diameter of 5–23 mm and 5–16 mm was observed with the ceftazidime-avibactam/aztreonam combination for Klebsiella pneumoniae and Escherichia coli, respectively, when compared to ceftazidime-avibactam and aztreonam disc tested alone. Out of 21 Enterobacterales studied, 21 (100%) isolates showed resistance to amoxicillin-clavulanate (≥32 μg/mL) and piperacillin-tazobactam (128 μg/mL), 12 (57.14%) isolates showed resistance to gentamicin (≥16 μg/mL), 5 (23.81%) isolates were resistant to amikacin (≥64 μg/mL), 21 (100%) isolates were resistant to ciprofloxacin (≥4 μg/mL), 19 (90.48%) isolates were resistant to cotrimoxazole (≥320 μg/mL), 21 (100%) isolates were resistant to cefepime (≥16 μg/mL) and 6 (28.57%) isolates were resistant to tigecycline (2 μg/mL). Conclusion: In the present study, 42.86% of Enterobacterales isolates showed synergism to the ceftazidime-avibactam/aztreonam combination. The optimal dosing strategy and in vivo efficacy of this combination need to be evaluated.

Phenotypic detection of carbapenem-resistant Enterobacterales in clinical isolates at a tertiary care hospital

Abstract Background: In the past decade, there has been a global emergence of carbapenem-resistant Gram-negative bacilli, especially Enterobacterales. Carbapenem resistance is attributed to the ability of the bacteria to produce carbapenemases. The aim of the study is to detect carbapenem-resistant Enterobacterales (CRE) in different clinical isolates and study carbapenemase production by phenotypic methods in CRE. Materials and Methods: A total of 379 Enterobacterales were isolated from different clinical samples from patients attending outpatient departments and admitted in wards and intensive care units (ICUs). They were tested for carbapenem resistance by Kirby–Bauer disk diffusion method and then tested for carbapenemase production by ethylenediaminetetraacetic acid (EDTA)–disk synergy test and Modified Carbapenem Inactivation Method (mCIM). Results: This study was conducted from February 2021 to August 2022. Out of 379 Enterobacterales, 70 (18.47%) were CRE, out of which maximum carbapenem resistance of 23.53% was shown by Klebsiella pneumoniae isolates. The maximum carbapenem resistance was seen in the age group of 16–45 years and the most number of CRE isolates were from ICUs. Phenotypic test results indicated that 54.28% (38/70) of isolates were positive for carbapenemase production by either of the phenotypic methods. Conclusion: About one-fifth of the Enterobacterales isolates were carbapenem resistant. This study highlights the use of phenotypic methods to detect carbapenemase production in CRE, which is responsible for multidrug resistance. This information is relevant for surveillance, to implement infection prevention and control practices and antibiotic policies.

Ceftazidime/avibactam combined with colistin: a novel attempt to treat carbapenem-resistant Gram-negative bacilli infection

BackgroundThe rapid global emergence and spread of carbapenem-resistant Gram-negative bacilli (CR-GNB) is recognized as a major public health concern, and there are currently few effective treatments for CR-GNB infection. The aim of this study was to investigate the clinical characteristics and outcomes of patients with CR-GNB infections treated with ceftazidime/avibactam (CAZ/AVI) combined with colistin from October 2019 to February 2023 in China.MethodsA total of 31 patients with CR-GNB infections were retrospectively identified using the electronic medical record system of Zhejiang Provincial People's Hospital.ResultsThirty-one patients were treated with CAZ/AVI combined with colistin. Respiratory tract infections (87%) were most common. The common drug-resistant bacteria encompass Klebsiella pneumonia (54.8%), Acinetobacter baumannii (29.0%), and Pseudomonas aeruginosa (16.1%). The 30-day mortality rate was 29.0%, and the 7-day microbial clearance rate was 64.5%. The inflammatory marker CRP changes, but not PCT and WBC, were statistically significant on days 7 and 14 after combination therapy. There were seven patients developing acute renal injury (AKI) after combination therapy and treating with continuous renal replacement therapy (CRRT). Two patients developed diarrhea.ConclusionThe combination of CAZ/AVI and colistin has potential efficacy in patients with CR-GNB infection, but more studies are needed to determine whether it can reduce 30-day mortality rates and increase 7-day microbial clearance. At the same time, the adverse reactions of combination therapy should not be ignored.

Secondary pulmonary infection and co-infection in elderly COVID-19 patients during the pandemics in a tertiary general hospital in Beijing, China.

Most people are infected with COVID-19 during pandemics at the end of 2022. Older patients were more vulnerable. However, the incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection is not well described in elderly hospitalized COVID-19 patients. We retrospectively reviewed the medical records of all elderly (≥65 years) hospitalized patients with laboratory-confirmed COVID-19 from December 1, 2022 to January 31, 2023. Demographics, underlying diseases, treatments, and laboratory data were collected. Univariate and multivariate logistic regression models were used to explore the risk factors associated with secondary bacterial, fungal or viral pulmonary infection and co-infection. A total of 322 older patients with COVID-19 were enrolled. The incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection was 27.3% (88/322) and 7.5% (24/322), respectively. The overall in-hospital mortality of all patients was 32.9% (106/322), and the in-hospital mortality among patients who acquired with secondary pulmonary infection and co-infection was 57.0% (57/100). A total of 23.9% (77/322) of patients were admitted to ICU within 48 h of hospitalization. The incidence of secondary pulmonary infection and co-infection among patients admitted to the ICU was 50.6% (39/77) and 13.0% (10/77), respectively. The overall in-hospital mortality of ICU patients was 48.1% (37/77), and the in-hospital mortality of ICU patients acquired with secondary pulmonary infection and co-infection was 61.4% (27/44). A total of 83.5% (269/322) of the included patients received empirical antibiotic therapy before positive Clinical Microbiology results. Influenza A virus (the vast majority were the H3N2 subtype) was the most common community acquired pathogen for co-infection. While A. baumannii, K. pneumoniae, and P. aeruginosa were the common hospital acquired pathogens for co-infection and secondary pulmonary infection. The incidence of Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections was high, and the mortality reached 76.9%. Predictors of secondary pulmonary infection and co-infection were ICU admission within 48 h of hospitalization, cerebrovascular diseases, critical COVID-19, and PCT > 0.5 ng/mL. The prognosis for elderly hospitalized COVID-19 patients with secondary pulmonary infection or co-infection is poor. The inflammatory biomarker PCT > 0.5 ng/mL played an important role in the early prediction of secondary pulmonary infection and co-infection in COVID-19 patients.

Detection of carbapenemase production in gram negative bacilli in medical and surgical intensive care unit patients in a tertiary care hospital

Background: Carbapenem-resistant Enterobacterales (CRE) are an urgent global public health problem. CRE infections are associated with high mortality and have limited available effective treatment. Carbapenemase enzymes are encoded by genes on mobile genetic elements, such as plasmids, which are highly transmissible between organisms and increase the potential spread of resistance. The study aim was to detect carbapenemase production in Gram negative bacilli by phenotypic (CarbaNP and mCIM only or in conjunction with eCIM) and genotypic (Xpert Carba-R) methods. Material and methods: The various clinical samples were processed as per standard recommended procedures. Identification and antibiotic susceptibility test were done by using GN cards and AST N280 &amp; AST N281 cards of Vitek 2 Compact (bioMérieux) respectively. Phenotypic (CarbaNP and mCIM only or in conjunction with eCIM) and genotypic (Xpert Carba-R) methods were used for detection of carbapenemases. Result: 144 carbapenem-resistant Gram-negative bacilli isolated from various ICUs includes Klebsiella pneumoniae 52.7% (76/144) followed by Escherichia coli 18.05% (26/144) and 15.9% (23/144) Acinetobacter baumannii. Phenotypic test (CarbaNP and mCIM and or in conjunction with eCIM) showed sensitivity of 90%, 100% and 93.75% respectively. Genotypic test of 40 isolates showed predominant expression of NDM in 82.5% (33/40) isolates followed by OXA-48 in 40% (16/40). Conclusion: The study showed mCIM as the most useful diagnostic test with less economic burden to the patients. There is an urgent need for more sensitive, rapid, highly precise and accurate genotypic test which is less expensive and less labor-intensive. Keywords: carbapenem resistant; Enterobacterales; mCIM; eCIM; Xpert Carba-R